Anthelmintics

Question 1

Classification

Answer 1

1. Drugs for roundworms (Nematodes) →anti-nematodal (AN)
2. Drugs for tapeworms (Cestodes) → anti-cestodal (AC)
3. Drugs for flukes (Trematodes) → anti-trematodal (AT)

Question 2

Benzimidazoles

Answer 2

AN,AC,AT
*inhibition of tubulin polymerisation leading to degenerative alterations. → impaired glucose uptake→ low energy→ immobalization→ death.
*Larval and adult stages
Albendazole (fumarate reductase)
*AC: Febantel, Fenbendazole, Netobimin (+SC), Albendazole, Ricobendazole, Mebendazole, Oxfendazole, Flubendazole, Luxabendazol.
*AT: Netobimin, Albendazole (adult liver fluke+others)
ii.Triclabendazole: best drug against liver fluke (fasciola hepatica) only for Trematodes
*Antitumour (Thiabendazole, +topical) ,antifungal,antiviral,PPI
*low GI absorption, inc. by feed intake, rumen is a reservoir.
*bile excretion + recycling
*PO (SC,topical_ , water soluble
*teratogenous , neuro+hepatotoxic
*multidrug resistance with endectocides and Levamisole.. (eq- large stronglyes,su-oesophagostomum sp.)
*WP: 8-14d meat , 3-5d milk

Question 3

Imidazothiazoles

Answer 3

AN

i. (Tetramisole)
ii. Levamisole
* agonist at nicotinic acetylcholine receptors→ spastic Paralysis
* vermicide : adults+larva (not for heartworm, kills too fast and causes severe SE)
* rapid absorption and excretion
* eq,fe and some ca - very senestive!
* SE: cholinergic type: salivation,tremous,ataxia,urination,defecation
* ANTIDOTE: Atropine
* cross resistance of Levamisole+Morantel
* PO,SC

Question 4

Tetrahydropyrimidines

Answer 4

AN
i. Pyrantel
ii. Morantel
*Cholinomimetic activity→ spastic Paralysis
*Adult+larval gut worm , no activity against migrating
*cross resistance with Levamisole
*pamoate salt :large intestine absorption!
* excreted rapidly in urine
*overdose:Cholinergic types of signs
*ANTIDOTE: Atropine
(ca,eq)

Question 5

Piperazines

Answer 5

AN

i. Piperazine
ii. Diethylcarbamazine (dog heartworm prevention! +IM)
* GABA agonistic effect→ flaccid paralysis (reversible -vermifuge)
* also block succinate production→ depleted of energy, expelled by peristalsis
* Ascaris parasites,hookworms
* rapidly absorbed in Gi , kidney excretion
* SE: vomiting, diarroea, ataxia
* PO

Question 6

Salicylanilides and substituted phenols

Answer 6

AT,AC (AN)

• Uncoupling of oxidative phosphorylation processes . act as protonophores→ H leakage→ dec. ATP production
• vermicide
• bile excretion , longer WP
• lower efficacy against young stages

i. Salicylanilide: Rafoxanide (AT, AN) ,Closantel (AN, AT),Niclosamide (AC) ,Oxyclozanide (AT, AC- bound to plasma proteins, mature flukes),Brotianide,Clioxanide
ii. Substituted phenols: Diamphenethide (AC,enter hepatocytes, special- excellent agaisnt YOUNG flukes, less for mature),

dichloriphene (AC) , hexachlorophene (AT)Niclofolan,Menichlofolan ,Nitroxinil (AT, must be SC->destroyed by Rumen bacteria), Diamphenethide (aromatic amide) Nitroscanate (AC, AN, not in in food producers and cats )
* SE: anorexia. high dosage:blindness, hyperthermia, convulsions and death
* adverse effect in severly stressed/poor conditioned animals/ severe infection
* PO

Question 7

Isoquinolin and benzazepin derivatives

Answer 7

AC
*Praziquantel and Epsiprantel
*Interfering IC Ca → regulation spastic paralysis, impaired motility and sucker function of cestode.
*mature and larva
*rapid, almost complete GI absorption, bile excretion.
*non-toxic
Best drugs against Echinococcosis!!

Question 8

Clorsulon (aminobenzene disulphonamide derivative)

Answer 8

AT

• Inhibits enzymes of the glycolytic pathway in liver flukes
• Bound to plasma proteins
• safe
• NOT for lactating cows
• PO- sheep, cow-SC (+ivermectin)
• Rumen is a reservoir

Question 9

Bunamidine salts

Answer 9

AC

• banned in Hungary
• Small animals, leads to digestion of tapeworms in the gut . (glucose uptake inhibition)
• most effective after fasting
• liver metabolism
• SE: vomiting , mild diarroea , cardiac arrest

Question 10

Emodepside

Answer 10

AN

• synaptic transmission inhibition via G protein→K efflux→ hyperpolarization→ Flaccid paralysis
• inhibition of egg laying
• effective against multidrug resistant nematodes to Ivermectin, Levamisole and Benzimidazoles.
• topically in combination with Praziquatel in cats. dogs:PO
• SE:rare and self limiting vomiting,diarroea,alopecia,shaking

Question 11

Melarsomine

Answer 11

AN

• not in Hungary
• heartworm adulticide!! not for late stage infections.
• crosses BBB
• excretion in bile and urine.
• inhibition of glutathione reductase+ glucose uptake and metabolism
• low TI: slight overdose: serious GI symptoms, bradycardia. high: pulmonary oedema

Question 12

Monepantel

Answer 12

AN

• for sheep
• acts on nicotinic receptors
• GI nematodes (including hypobiotic larvae)
• active against nematodes that are resistant to other anthelmintic
• Bile excretion
• PO

Question 13

macrocyclic lactones

Answer 13

AN

• both ecto and endoparacidal , arthropods (flea,lice,mite) and adult+immature nematodes (+heartworm)
• inhibitor of glutamate-gated chloride channel receptors in nerve cells→ influx→paralysis
• GABAergic effect: GABA release.
• Lipophilic, accumilation,long lasting effect.
• contraindicated in calves and foals in less 4 months.
• safety depends on p-glycoprotein activity in the BBB.
• SE: CNS depression in cattle,Collies, Bobtails, Australian shepherd in ivermectin, doramectin, abamectin, moxidectin. (newer compounds selamectin and milbemycinoxime are not causing)
• PO, topically
• ANTIDOTE: Picrotoxin 1% → infusion
• multidrug resistance with BZ’s and Levamisole.
  i. Avermectins: Abamectin,Ivermectin (toxic to Collies),Doramectin,Eprinomectin,Selamectin (not for food producing)
  ii. Milbemycins: Milbemycin oxime,Moxidectin